title: A novel resveratrol analogue, HS-1793, inhibits hypoxia-induced HIF-1α and VEGF expression, and migration in human prostate cancer cells.
abstract: In many studies, resveratrol has been shown to have a chemopreventive effect in various types of cancer cells. However, the biological activity of resveratrol is limited by its photosensitivity and metabolic instability. This study investigated the effects of a novel analogue of resveratrol, HS-1793, on the expression of HIF-1α and vascular endothelial growth factor (VEGF) in PC-3 human prostate cancer cells. Hypoxic condition induced HIF-1α protein level in PC-3 cells in a time-dependent manner, and treatment with HS-1793 markedly decreased HIF-1α expression levels. HS-1793 also inhibited VEGF level. Mechanistically, HS-1793 inhibited HIF-1α and VEGF expression through multiple mechanisms. Firstly, HS-1793 inhibited phosphorylation of PI3K and Akt in PC-3 cells. Furthermore, HS-1793 substantially induced HIF-1α protein degradation through the proteasome pathway. Finally, HS-1793 inhibited hypoxia-induced PC-3 cell migration. These data suggest that HS-1793 may inhibit human prostate cancer progression and angiogenesis by inhibiting the expression of HIF-1α and VEGF. Moreover, HS-1793 showed more potent effects than resveratrol on the cytotoxic effects on PC-3 cells. Taken together, these results implied that HS-1793, a novel analogue of resveratrol, may be a new potent chemopreventive agent against human prostate cancer cells.
authors.affiliation: Department of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Kim
authors.forename: Mohammad Akbar
authors.initials: MA
authors.lastname: Hossain
authors.forename: Min Young
authors.initials: MY
authors.lastname: Kim
authors.forename: Jin-Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Jeong-Hyun
authors.initials: JH
authors.lastname: Yoon
authors.forename: Hong Suk
authors.initials: HS
authors.lastname: Suh
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
authors.forename: Nam Deuk
authors.initials: ND
authors.lastname: Kim
mesh_terms: D015687:Cell Hypoxia / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000096:biosynthesis / Q000378:metabolism*; D008297:Male; D009284:Naphthols / Q000494:pharmacology*; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012118:Resorcinols / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: C523393:4-(6-hydroxy-2-naphthyl)-1,3-benzenediol; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009284:Naphthols; D012118:Resorcinols; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A